tbuckley/cabot-search huggingface dataset:
Potassium homeostasis – Physiology and pharmacology in a clinical context
Authors: Ralph Kettritz, Johannes Loffing
Journal: Pharmacology & Therapeutics (2023)

Membrane voltage controls the function of excitable cells and is mainly a consequence of the ratio between the extra- and intracellular potassium concentration. Potassium homeostasis is safeguarded by balancing the extra−/intracellular distribution and systemic elimination of potassium to the dietary potassium intake. These processes adjust the plasma potassium concentration between 3.5 and 4.5 mmol/L. Several genetic and acquired diseases but also pharmacological interventions cause dyskalemias that are associated with increased morbidity and mortality. The thresholds at which serum K+ not only associates but also causes increased mortality are hotly debated. We discuss physiologic, pathophysiologic, and pharmacologic aspects of potassium regulation and provide informative case vignettes. Our aim is to help clinicians, epidemiologists, and pharmacologists to understand the complexity of the potassium homeostasis in health and disease and to initiate appropriate treatment strategies in dyskalemic patients.
Viral and antibody dynamics of acute infection with SARS-CoV-2 omicron variant (B.1.1.529): a prospective cohort study from Shenzhen, China
Authors: Yang Yang, Liping Guo, Jing Yuan, Zhixiang Xu, Yuchen Gu, Jiaqi Zhang, Yuan Guan, Jinhu Liang, Hongzhou Lu, Yingxia Liu
Journal: The Lancet Microbe (2023)

Elucidating viral dynamics within the host is important for designing public health measures against SARS-CoV-2, particularly during the early stages of infection when transmission potential rapidly increases. We aimed to analyse the viral and antibody dynamics of the omicron variant in relation to symptom onset or laboratory confirmation and replication dynamics throughout the infection course.
Effectiveness of previous infection-induced and vaccine-induced protection against hospitalisation due to omicron BA subvariants in older adults: a test-negative, case-control study in Quebec, Canada
Authors: Sara Carazo, Danuta M Skowronski, Marc Brisson, Chantal Sauvageau, Nicholas Brousseau, Judith Fafard, Rodica Gilca, Denis Talbot, Manale Ouakki, Yossi Febriani, Geneviève Deceuninck, Philippe De Wals, Gaston De Serres
Journal: The Lancet Healthy Longevity (2023)

Older adults (aged ≥60 years) were prioritised for COVID-19 booster vaccination due to severe outcome risk, but the risk for this group is also affected by previous SARS-CoV-2 infection and vaccination. We estimated vaccine effectiveness against omicron-associated hospitalisation in older adults by previously documented infection, time since last immunological event, and age group.This was a population-based test-negative case-control study done in Quebec, Canada, during BA.1 dominant (December, 2021, to March, 2022), BA.2 dominant (April to June, 2022), and BA.4/5 dominant (July to November, 2022) periods using provincial laboratory, immunisation, hospitalisation, and chronic disease surveillance databases. We included older adults (aged ≥60 years) with symptoms associated with COVID-19 who were tested for SARS-CoV-2 in acute-care hospitals. Cases were defined as patients who were hospitalised for COVID-19 within 14 days after testing positive; controls were patients who tested negative. Analyses spanned 3-14 months after last vaccine dose or previous infection. Logistic regression models compared COVID-19 hospitalisation risk by mRNA vaccine dose and previous infection versus unvaccinated and infection-naive participants.Between Dec 26, 2021, and Nov 5, 2022, we included 174 819 specimens (82 870 [47·4%] from men and 91 949 [52·6%] from women; from 8455 cases and 166 364 controls), taken from 2951 cases and 48 724 controls in the BA.1 period; 1897 cases and 41 702 controls in the BA.2 period; and 3607 cases and 75 938 controls in the BA.4/5 period. In participants who were infection naive, vaccine effectiveness against hospitalisation improved with dose number, consistent with a shorter median time since last dose, but decreased with more recent omicron subvariants. Four-dose vaccine effectiveness was 96% (95% CI 93-98) during the BA.1 period, 84% (81-87) during the BA.2 period, and 68% (63-72) during the BA.4/5 period. Regardless of dose number (two to five doses) or timing since previous infection, hybrid protection was more than 90%, persisted for at least 6-8 months, and did not decline with age.Older adults with both previous SARS-CoV-2 infection and two or more vaccine doses appear to be well protected for a prolonged period against hospitalisation due to omicron subvariants, including BA.4/5. Ensuring that older adults who are infection naive remain up to date with vaccination might reduce COVID-19 hospitalisations most efficiently.Ministère de la Santé et des Services Sociaux du Québec.For the French translation of the abstract see Supplementary Materials section.
Mitophagy in the retina: Viewing mitochondrial homeostasis through a new lens
Authors: Juan Ignacio Jiménez-Loygorri, Rocío Benítez-Fernández, Álvaro Viedma-Poyatos, Juan Zapata-Muñoz, Beatriz Villarejo-Zori, Raquel Gómez-Sintes, Patricia Boya
Journal: Progress in Retinal and Eye Research (2023)

Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of the highest metabolic rates body-wide and is constantly exposed to photooxidative damage and external stressors. Mitophagy is the selective autophagic degradation of mitochondria within lysosomes, and can be triggered by distinct stimuli such as mitochondrial damage or hypoxia. Here, we review the importance of mitophagy in retinal physiology and pathology. In the developing retina, mitophagy is essential for metabolic reprogramming and differentiation of retina ganglion cells (RGCs). In basal conditions, mitophagy acts as a quality control mechanism, maintaining a healthy mitochondrial pool to meet cellular demands. We summarize the different autophagy- and mitophagy-deficient mouse models described in the literature, and discuss the potential role of mitophagy dysregulation in retinal diseases such as glaucoma, diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration. Finally, we provide an overview of methods used to monitor mitophagy in vitro, ex vivo, and in vivo. This review highlights the important role of mitophagy in sustaining visual function, and its potential as a putative therapeutic target for retinal and other diseases.
The promising application of cell-cell interaction analysis in cancer from single-cell and spatial transcriptomics
Authors: Xinyi Wang, Axel A. Almet, Qing Nie
Journal: Seminars in Cancer Biology (2023)

Cell-cell interactions instruct cell fate and function. These interactions are hijacked to promote cancer development. Single-cell transcriptomics and spatial transcriptomics have become powerful new tools for researchers to profile the transcriptional landscape of cancer at unparalleled genetic depth. In this review, we discuss the rapidly growing array of computational tools to infer cell-cell interactions from non-spatial single-cell RNA-sequencing and the limited but growing number of methods for spatial transcriptomics data. Downstream analyses of these computational tools and applications to cancer studies are highlighted. We finish by suggesting several directions for further extensions that anticipate the increasing availability of multi-omics cancer data.
Multiple hepatic cysts in an adult male
Authors: Alberto Zanetto, Filippo Pelizzaro, Elena Bellan, Marta Sbaraglia
Journal: Journal of Hepatology (2023)

A 59-year-old male with an uneventful past medical history was admitted to our service due to epigastric pain, inappetence, and weight loss. The symptoms started after a recent trip to Morocco to visit his family. He denied any exposure to unusual plants or animals. Vitals were normal. Physical examination showed an enlarged liver. Labs demonstrated normocytic anemia (hemoglobin 12 g/dl), slight elevation of AST (70 U/L, with an upper limit of normal [ULN] of 45 U/L), normal ALT, a significant increase in GGT (1,137 U/L; ULN: 65 U/L) and ALP (428 U/L; ULN: 128 U/L), normal bilirubin, and a modest increase in C-reactive protein (21 mg/L; ULN: 6 mg/L). CEA, AFP, and CA 19-9 were normal, while HBV and HCV serology were negative. Upper endoscopy was normal; colonoscopy showed a single 10 mm adenoma in the caecum. Liver ultrasound showed multiple spheric lesions measuring between 1 and 6 cm, some appearing as unilocular anechoic spaces with thin walls reminiscent of simple hepatic cysts, whilst others appeared as relatively hypoechoic lesions with mural thickening, hyperechoic walls, and debris-containing fluid, without signal flow on color Doppler (Fig. 1, left ). An extensive microbiological work-up including Echinococcus, Entamoeba, and TBC was ordered. Based on the clinical picture and liver ultrasound suggestive of hepatic cyst infection, the patient was treated with metronidazole and underwent cyst aspiration (with evacuation of dense, chocolate-colored fluid) and percutaneous biopsy of one of these lesions (Fig. 1, right). The C-reactive protein decreased to normal values, and he was discharged to the outpatient service.
Addressing Ancestry and Sex Bias in Pharmacogenomics
Authors: Manuel Corpas, Moneeza K. Siddiqui, Opeyemi Soremekun, Rohini Mathur, Dipender Gill, Segun Fatumo
Journal: The Annual Review of Pharmacology and Toxicology (2023)

The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase
Multifunctional Fiber‐Based Optoacoustic Emitter as a Bidirectional Brain Interface
Authors: Nan Zheng, Ying Jiang, Shan Jiang, Jongwoon Kim, Guo Chen, Yueming Li, Ji‐Xin Cheng, Xiaoting Jia, Chen Yang
Journal: Advanced Healthcare Materials (2023)

A bidirectional brain interface with both "write" and "read" functions can be an important tool for fundamental studies and potential clinical treatments for neurological diseases. Herein, a miniaturized multifunctional fiber-based optoacoustic emitter (mFOE) is reported thatintegrates simultaneous optoacoustic stimulation for "write" and electrophysiology recording of neural circuits for "read". Because of the intrinsic ability of neurons to respond to acoustic wave, there is no requirement of the viral transfection. The orthogonality between optoacoustic waves and electrical field provides a solution to avoid the interference between electrical stimulation and recording. The stimulation function of the mFOE is first validated in cultured ratcortical neurons using calcium imaging. In vivo application of mFOE for successful simultaneous optoacoustic stimulation and electrical recording of brain activities is confirmed in mouse hippocampus in both acute and chronical applications up to 1 month. Minor brain tissue damage is confirmed after these applications. The capability of simultaneous neural stimulation and recording enabled by mFOE opens up new possibilities for the investigation of neural circuits and brings new insights into the study of ultrasound neurostimulation.
Cold snare endoscopic mucosal resection for colon polyps: a systematic review and meta-analysis
Authors: Mohamed Abdallah, Khalid Ahmed, Daniyal Abbas, Mouhand F. H. Mohamed, Gaurav Suryawanshi, Nicholas McDonald, Natalie Wilson, Shifa Umar, Aasma Shaukat, Mohammad Bilal
Journal: Endoscopy (2023)

Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %-17.4 %, I2 = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %-35.7 %, I2 = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %-46.7 %, I2 = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %-9.9 %, I2 = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %-4.5 %, I2 = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %-2.7 %, I2 = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %-1.3 %, I2 = 0 %) and 0.6 % (95 %CI 0.3 %-1.4 %, I2 = 0 %), respectively. CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.
TBCK syndrome: a rare multi-organ neurodegenerative disease
Authors: Emily L. Durham, Rajesh Angireddy, Aaron Black, Ashley Melendez-Perez, Sarina Smith, Elizabeth M. Gonzalez, Kristen G. Navarro, Abdias Díaz, Elizabeth J.K. Bhoj, Kaitlin A. Katsura
Journal: Trends in Molecular Medicine (2023)
Tube Feed or Not Tube Feed: Ethics beyond the Consult Question
Authors: Joan Henriksen, Nina Current, Scott Nelson
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:“I Don’t Want to Gain Weight!” The Ethics of Tube Feeding Over the Objection of a Patient with Anorexia Nervosa Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Canceling Tuskegee
Authors: Jerry Menikoff
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Response to Open Peer Commentaries on “Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded into Care”This article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in Care Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Participation in Pragmatic Clinical Trials: A Matter of Physicians’ Professional Ethics?
Authors: Sabine Salloch
Journal: The American Journal of Bioethics (2023)

"Participation in Pragmatic Clinical Trials: A Matter of Physicians’ Professional Ethics?." The American Journal of Bioethics, 23(8), pp. 79–80This article refers to:Do Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Pragmatic Research and Clinical Duties: Solutions Through Precision AI-Enabled Clinically Embedded Research
Authors: Emma Friedman, Matthew John Baumann, Shruti Sehgal, Justin Starren, Russell Steans, Amanda Venables, Kelly Michelson
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in CareDo Clinicians Have a Duty to Participate in Pragmatic Clinical Trials? Additional informationFundingThis work was supported by the Greenwall Foundation. This work is also funded by grant 2UL1TR001422 from the National Institutes of Health.
Emulated trial investigating effects of multiple treatments: estimating combined effects of mucoactive nebulisers in cystic fibrosis using registry data
Authors: Emily Granger, Gwyneth Davies, Ruth H Keogh
Journal: Thorax (2023)

Introduction People with cystic fibrosis (CF) are often on multiple long-term treatments, including mucoactive nebulisers. In the UK, the most common mucoactive nebuliser is dornase alfa (DNase). A common therapeutic approach for people already on DNase is to add hypertonic saline (HS). The effects of DNase and HS used alone have been studied in randomised trials, but their effects in combination have not. This study investigates whether, for people already prescribed DNase, adding HS has additional benefit for lung function or use of intravenous antibiotics. Methods Using UK CF Registry data from 2007 to 2018, we emulated a target trial. We included people aged 6 years and over who were prescribed DNase without HS for 2 years. We investigated the effects of combinations of DNase and HS over 5 years of follow-up. Inverse-probability-of-treatment weighting was used to control confounding. The period predated triple combination CF transmembrane conductance regulator modulators in routine care. Results 4498 individuals were included. At baseline, average age and forced expiratory volume in 1 s (FEV 1 %) predicted were 21.1 years and 69.7 respectively. During first year of follow-up, 3799 individuals were prescribed DNase alone; 426 added HS; 57 switched to HS alone and 216 were prescribed neither. We found no evidence that adding HS improved FEV 1 % at 1–5 years, or use of intravenous antibiotics at 1–4 years, compared with DNase alone. Conclusion For individuals with CF prescribed DNase, we found no evidence that adding HS had an effect on FEV 1 % or prescription of intravenous antibiotics. Our study illustrates the emulated target trial approach using CF Registry data.
Pulmonary telerehabilitation vs. conventional pulmonary rehabilitation – a secondary responder analysis
Authors: Henrik Hansen, Andre Torre, Thomas Kallemose, Charlotte Suppli Ulrik, Nina Skavlan Godtfredsen
Journal: Thorax (2023)

Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups in 134 patients with COPD randomised (1:1) to either home-based PTR or traditional hospital-based outpatient PR. Difference between PTR and PR on 6MWD response proportion could not be shown at 10 (OR=0.72, CI=0.34 to 1.51, p=0.381) or 62 weeks (OR=1.12, CI=0.40 to 3.14, p=0.834). While the evidence and knowledge of PTR accumulate, outpatient supervised PR for now remains the standard of care, with home-based PTR as a strong secondary option for those unable to attend out-patient programmes.
Effects of Meditation Training and Non-Native Language Training on Cognition in Older Adults
Authors: Harriet Demnitz-King, Florence Requier, Tim Whitfield, Marco Schlosser, Julie Gonneaud, Caitlin Ware, Thorsten Barnhofer, Nina Coll-Padros, Sophie Dautricourt, Marion Delarue, Olga M. Klimecki, Léo Paly, Eric Salmon, Ann-Katrin Schild, Miranka Wirth, Eric Frison, Antoine Lutz, Gaël Chételat, Fabienne Collette, Natalie L. Marchant, Florence Allais, Claire André, Eider Arenaza-Urquijo, Julien Asselineau, Sebastian Baez Lugo, Martine Batchelor, Axel Beaugonin, Alexandre Bejanin, Maelle Botton, Pierre Champetier, Anne Chocat, Robin De Flores, Vincent De La Sayette, Pascal Delamilleure, Stéphanie Egret, Hélene Espérou, Francesca Felisatti, Eglantine Ferrand-Devouges, Antoine Garnier-Groussard, Francis Gheysen, Marc Heidmann, Anne Hendy, Thien Huong Tran, Agathe Joret Philippe, Elizabeth Kuhn, Brigitte Landeau, Gwendoline Le Du, Valérie Lefranc, Florence Mezenge, Inés Moulinet, Valentin Ourry, Cassandre Palix, Anne Quillard, Géraldine Rauchs, Stéphane Rehel, Corrine Schwimmer, Siya Sherif, Clémence Tomadesso, Edelweiss Touron, Matthieu Vanhoutte
Journal: JAMA Network Open (2023)

Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults.
Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Eileen M. Boyle, Patrick Blaney, James H. Stoeckle, Yubao Wang, Hussein Ghamlouch, Dylan Gagler, Marc Braunstein, Louis Williams, Avital Tenenbaum, Ariel Siegel, Xiaoyi Chen, Gaurav Varma, Jason Avigan, Alexander Li, Monica Jinsi, David Kaminetzsky, Arnaldo Arbini, Lydia Montes, Jill Corre, Even H. Rustad, Ola Landgren, Francesco Maura, Brian A. Walker, Michael Bauer, Benedetto Bruno, Aristotelis Tsirigos, Faith E. Davies, Gareth J. Morgan
Journal: Clinical Cancer Research (2023)

Chromosome 1 (chr1) copy-number abnormalities (CNA) and structural variants (SV) are frequent in newly diagnosed multiple myeloma (NDMM) and are associated with a heterogeneous impact on outcomes, the drivers of which are largely unknown.A multiomic approach comprising CRISPR, gene mapping of CNAs and SVs, methylation, expression, and mutational analysis was used to document the extent of chr1 molecular variants and their impact on pathway utilization.We identified two distinct groups of gain(1q): focal gains associated with limited gene-expression changes and a neutral prognosis, and whole-arm gains, which are associated with substantial gene-expression changes, complex genetics, and an adverse prognosis. CRISPR identified a number of dependencies on chr1 but only limited variants associated with acquired CNAs. We identified seven regions of deletion, nine of gain, three of chromothripsis (CT), and two of templated insertion (TI), which contain a number of potential drivers. An additional mechanism involving hypomethylation of genes at 1q may contribute to the aberrant gene expression of a number of genes. Expression changes associated with whole-arm gains were substantial and gene set enrichment analysis identified metabolic processes, apoptotic resistance, signaling via the MAPK pathway, and upregulation of transcription factors as being key drivers of the adverse prognosis associated with these variants.Multiple layers of genetic complexity impact the phenotype associated with CNAs on chr1 to generate its associated clinical phenotype. Whole-arm gains of 1q are the critically important prognostic group that deregulate multiple pathways, which may offer therapeutic vulnerabilities.